The world is awash in antibiotics. Once used for a limited number of
diseases, they are now called upon to treat even the common cold. The
resistance that bacteria have evolved against these medications has
given rise to a host of superbugs and strains of infectious diseases
that our antibiotics can’t treat.

For
all three of his summers at Brown, Daniel Greenwald researched
solutions to this global threat. Growing up in Madison, Wisconsin, he
was a Legos kid, building something, taking it apart, and then building
something new. No wonder that, as a freshman at Brown, he took organic
chemistry and loved it. “I’d found where I belonged,” he says.
Constructing the solution of antibacterial resistance was like building
something out of Legos: all you have to do is connect the pieces.

Working with a Jason Sello, a graduate student who soon became an
assistant professor of chemistry, Greenwald built molecules in the lab,
a challenge that can take weeks. Greenwald used a process called the
Ugi reaction, in which a molecule’s elements are fused together all at
once. Using this approach, he could create a new compound overnight.

In the end, with the support of Brown’s Royce Fellows Program, which
provides research grants to undergraduates, Greenwald created more than
fifty different compounds, each one a kind of Lego structure he then
studied and tested. One of the first compounds Greenwald and his
colleagues made was the most successful. Called BU-005, it’s a small
molecule that attacks the thousands of efflux pumps found in a
bacterium cell. When an antibiotic penetrates a bacterium cell, the
efflux pumps, located in the cell membrane, pump it out, saving the
bacterium’s life. BU-005 was three times more effective than similar
compounds at shutting down the pumps. It’s still very early, but
Greenwald hopes that in the long term BU-005 may be able to work
against antibiotic-resistant strains of tuberculosis and
Staphylococcus. He published the results of his research, in
collaboration with Professor Sello and his graduate student colleagues,
in the December 2011 issue of Bioorganic and Medicinal Chemistry. “By
becoming a published research scientist, I lived out the dream I had as
a little kid,” Greenwald says.

Greenwald next plans to work in Boston with a consulting company that
helps drug companies set prices for its products. “The appeal is being
able to apply the same methodology and academic rigor to the world of
business,” he says. “I don’t feel like I’m leaving the science behind.”

Photo by Dana Smith

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The Brown Alumni Magazine is published bimonthly, in print since 1900.